ethyl 4-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate | 187998-90-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 4-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate
• 英文别名: ethyl 4-trifluoromethyl-2-(4-(trifluoromethyl)phenyl)thiazole-5-carboxylate
• CAS: 187998-90-9
• 化学式: C₁₄H₉F₆NO₂S
• 分子量: 369.287
• InChiKey: KRHVHFJQSVHZFH-UHFFFAOYSA-N

物化性质

• 熔点：
  80-82 °C
• 沸点：
  388.2±52.0 °C(predicted)
• 密度：
  1.426±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  67.4
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  ethyl 4-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate 在 lithium hydroxide 、 sodium hydroxide 、 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 39.0h， 生成 2-methyl-2-[4-{[(4-trifluoromethyl-2-[4-trifluoromethylphenyl]-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid
  参考文献：
  名称：

  Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents

  摘要：

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.

  DOI：

  10.1021/jm058056x
• 作为产物：
  描述：

  2-氯-4,4,4-三氟乙酰乙酸乙酯 、 4-(三氟甲基)硫代苯甲酰胺 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以13%的产率得到ethyl 4-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate
  参考文献：
  名称：

  Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents

  摘要：

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.

  DOI：

  10.1021/jm058056x

文献信息

• Diverse Trifluoromethyl Heterocycles from a Single Precursor
  作者：Mark A. Honey、Raffaele Pasceri、William Lewis、Christopher J. Moody

  DOI：10.1021/jo202201w

  日期：2012.2.3

  Ethyl 2-diazo-4,4,4-trifluoro-3-oxobutanoate is a highly versatile intermediate for the synthesis of a wide range of trifluoromethyl heterocycles. With the use of rhodium(II) or copper(II) catalyzed carbene X-H insertion reactions as key steps, a diverse set of trifluoromethyl-oxazoles, -thiazoles, -imidazoles, -1,2,4-triazines, and -pyridines are available from the diazoketoester, either directly in a single step or with just one additional step.
• NEW CARBOXAMIDES WITH ANTIFUNGAL ACTIVITY
  申请人：J. URIACH & CIA. S.A.

  公开号：EP0783502A1

  公开（公告）日：1997-07-16
• US5888941A
  申请人：——

  公开号：US5888941A

  公开（公告）日：1999-03-30
• [EN] NEW CARBOXAMIDES WITH ANTIFUNGAL ACTIVITY<br/>[FR] NOUVEAUX CARBOXAMIDES A ACTIVITE ANTIFONGIQUE
  申请人：J. URIACH & CIA. S.A.

  公开号：WO1997005131A1

  公开（公告）日：1997-02-13

  (EN) Compounds of general formula (I) and their salts and solvates are antifungal agents and as such are useful in the treatment of various fungal infections. Pharmaceutical compositions including these compounds and processes for their preparation are also provided.(FR) Les composés de la formule générale (I) et leurs sels et solvates sont des agents antifongiques. Ils sont utiles dans le traitement de différentes infections fongiques. L'invention concerne également des compositions pharmaceutiques comprenant ces composés et des procédés permettant leur préparation.
• Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents
  作者：Michael L. Sierra、Véronique Beneton、Anne-Bénédict Boullay、Thierry Boyer、Andrew G. Brewster、Frédéric Donche、Marie-Claire Forest、Marie-Hélène Fouchet、Françoise J. Gellibert、Didier A. Grillot、Millard H. Lambert、Alain Laroze、Christelle Le Grumelec、Jean Michel Linget、Valerie G. Montana、Van-Loc Nguyen、Edwige Nicodème、Vipul Patel、Annie Penfornis、Olivier Pineau、Danig Pohin、Florent Potvain、Géraldine Poulain、Cécile Bertho Ruault、Michael Saunders、Jérôme Toum、H. Eric Xu、Robert X. Xu、Pascal M. Pianetti

  DOI：10.1021/jm058056x

  日期：2007.2.1

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.